(Thio)nicotinamide ribofuranoside salts and compositions, methods of making, and uses thereof

A method of making crystalline nicotinamide-β-D-ribofuranoside bromide of formula O-Ia

• or crystalline thionicotinamide-β-D-ribofuranoside bromide of formula S-Ia
• comprising at least step (A):
• (A) subjecting a tetra-O-acyl-β-D-ribofuranose of formula II
• wherein each R is independently selected from acyl, to hydrogen bromide in acetic acid to yield a tri-O-acyl-β-D-ribofuranoside bromide of formula III
• and step (B):
• (B) reacting the compound of formula III with nicotinamide of formula O—IV
• to obtain a nicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula O-Va:
• or reacting the compound of formula III with thionicotinamide of formula S—IV
• to obtain a thionicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula S-Va:
• wherein in step (B) the compound of formula O—IV or formula S—IV is used in an excess compared to the compound of formula III.

A method of making crystalline nicotinamide-β-D-ribofuranoside bromide of formula O-Ia

• or crystalline thionicotinamide-β-D-ribofuranoside bromide of formula S-Ia
• comprising at least step (A):
• (A) subjecting a tetra-O-acyl-β-D-ribofuranose of formula II
• wherein each R is independently selected from acyl, to hydrogen bromide in acetic acid to yield a tri-O-acyl-β-D-ribofuranoside bromide of formula III
• and step (B):
• (B) reacting the compound of formula III with nicotinamide of formula O—IV
• to obtain a nicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula O-Va:
• or reacting the compound of formula III with thionicotinamide of formula S—IV
• to obtain a thionicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula S-Va:
• wherein step (B) is carried out by adding nicotinamide of formula O—IV dissolved in acetonitrile or thionicotinamide of formula S—IV dissolved in acetonitrile to a solution comprising the compound of formula III and acetonitrile, hydrogen bromide and acetic acid, and
• wherein the temperature of the nicotinamide of formula O—IV in acetonitrile or the thionicotinamide of formula S—IV in acetonitrile is kept in a range of from 50° C. to 75° C. and the temperature of the solution comprising the compound of formula III is kept in a temperature range of from −10° C. to 30° C.

A method of making crystalline nicotinamide-β-D-ribofuranoside bromide of formula O-Ia

• or crystalline thionicotinamide-β-D-ribofuranoside bromide of formula S-Ia
• comprising at least step (A):
• (A) subjecting a tetra-O-acyl-β-D-ribofuranose of formula II
• wherein each R is independently selected from acyl, to hydrogen bromide in acetic acid to yield a tri-O-acyl-β-D-ribofuranoside bromide of formula III
• step (B):
• (B) reacting the compound of formula III with nicotinamide of formula O—IV
• to obtain a nicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula O-Va:
• or reacting the compound of formula III with thionicotinamide of formula S—IV
• to obtain a thionicotinamide-2,3,5-tri-O-acyl-β-D-ribofuranoside bromide of formula S-Va:
• step (C):
• (C) purifying the compound of formula O-Va or the compound of formula S-Va obtained in step (B), optionally by crystallization, re-crystallization, or crystallization and re-crystallization,
• step (D):
• (D) deprotecting the compound of formula O-Va or formula S-Va obtained in step (B) or step (C) by removing the R groups using hydrogen bromide in acetic acid to give the compound of formula O-Ia or formula S-Ia;
• and step (E):
• (E) purifying the compound of formula O-Ia or formula S-Ia obtained in step (D) by crystallization, re-crystallization, or crystallization and re-crystallization.